The extravascular distribution of plasma proteins is effected by both the selectivity of the vascular barrier and an interlinked matrix of collagen and glycosaminoglycans within the interstitium. In our present work, we found that changes in the extravascular mass of albumin and IgG following interstitial edema did not parallel changes in the lymph protein concentration in both skin and skeletal muscle. Our hypothesis is that plasma proteins distribute within two compartments: a non-restrictive one which exchanges freely with lymph and a restrictive one which sterically and electrostatically restrict the movement and distribution of plasma proteins. There is transvascular protein flux into both compartments; however, the protein flux into the restrictive compartment is predominately diffusion, while that into the lymph compartment is predominately convective. The transvascular transport into the restrictive compartment depends mainly upon the charge of the plasma protein, while that into the lymph compartment depends upon size. The effects of the restrictive compartment on protein transport are more predominate in skin, with its high collagen content, than skeletal muscle. The specific activity of tracer albumin and IgG will be measured in lymph and tissue at different times following a constant plasma activity to determine the relative sizes and turnover rates of the two compartments. Data from skin will be compared to data from skeletal muscle to determine if the two compartment behavior is more predominant in skin. Data obtained following plasmapheresis will be compared to data obtained after increased venous pressure to test the hypothesis that decreasing plasma oncotic pressure effects the restrictive compartment while increasing microvascular pressure effects the non-restrictive compartment. The equilibration of monomeric and dimeric albumin of different isoelectric points will be studied to determine the importance of charge on the extravascular distribution of plasma proteins. The initial tissue uptake rate of monomeric and dimeric albumins of different isoelectric points will be compared to the steady-state lymph-to-plasma concentration ratios to determine the relationship between charge, microvascular selectivity, and lymph concentrations. These results will provide information on the role of the interstitial matrix in tissue fluid balance and the relationship between lymph protein concentrations and microvascular selectivity.